Carla Lou Morgenroth, Philipp Kleymann, Stephan Ripke, Swapnil Awasthi, Elias Wagner, Tatiana Oviedo-Salcedo, Cynthia Okhuijsen-Pfeifer, Jurjen J. Luykx, Marte Z. van der Horst, Alkomiet Hasan, Felix Bermpohl, Stefan Gutwinski, Stefanie Schreiter
- Obsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clo-
zapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive–compulsive disorder (OCD) in this subgroup
and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores
(PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was
recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom
Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global
Assessment of Functioning Scale (GAF) and Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). Participants were divided
into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS
analyses were performed to evaluate theObsessive–compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clo-
zapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive–compulsive disorder (OCD) in this subgroup
and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores
(PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was
recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom
Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global
Assessment of Functioning Scale (GAF) and Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). Participants were divided
into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS
analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted
predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabo-
lism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6%
and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in
years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant cor-
relation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity
and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ,
CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics
of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment dura-
tion in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ
metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings
and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to
the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and
PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ
plasma level, is relevant for OCD development.…